Effects of an Intravitreal Daunomycin Implant on Experimental Proliferative Vitreoretinopathy: Simultaneous Pharmacokinetic and Pharmacodynamic Evaluations

Rahimy, Mohamad H.; Peyman, G.A.; Fernandes, Mariana Lima; El-Sayed, Saber H; Luo, Qiuhua; Borhani, Hesamodin

doi:10.1089/jop.1994.10.561

Cited by 22 publications

(9 citation statements)

References 3 publications

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“…[5] Indeed, in another in vivo study Peyman and colleagues found that sustained release (21 days) of DNR in vitreous at a concentration of 5~60 ng/mL resulted insignificant inhibition of PVR development. [29] Our previous work [10, 11] suggests that this pSi-based DNR delivery system may provide a sustained DNR level in vitreous because the DNR loaded pSi particles was seen for 2–3 months following a single intravitreal injection.…”

Section: Discussionmentioning

confidence: 99%

Tunable sustained intravitreal drug delivery system for daunorubicin using oxidized porous silicon

Hou

Nieto

et al. 2014

Journal of Controlled Release

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Daunorubicin (DNR) is an effective inhibitor of an array of proteins involved in neovascularization, including VEGF and PDGF. These growth factors are directly related to retina scar formation in many devastating retinal diseases. Due to the short vitreous half-life and narrow therapeutic window, ocular application of DNR is limited. It has been shown that a porous silicon (pSi) based delivery system can extend DNR vitreous residence from a few days to 3 months. In this study we investigated the feasibility of altering the pore size of the silicon particles to regulate the payload release. Modulation of the etching parameters allowed control of the nano-pore size from 15 nm to 95 nm. In vitro studies showed that degradation of pSi O2 increased with increasing pore size and the degradation of pSi O2 was approximately constant for a given particle type. The degradation of pSi O2 with 43 nm pores was significantly greater than the other two particles with smaller pores, judged by observed and normalized mean Si concentration of the dissolution samples (44.2±8.9 vs 25.7±5.6 or 21.2±4.2 µg/mL, p<0.0001). In vitro dynamic DNR release revealed that pSiO2-CO2H:DNR (Porous silicon dioxide with covalent loading of daunorubicin) with large pores (43 nm) yielded a significantly higher DNR level than particles with 15 or 26 nm pores (13.5±6.9 ng/mL vs. 2.3±1.6 ng/mL and 1.1±0.9 ng/mL, p<0.0001). After two months of in vitro dynamic release, 54% of the pSiO2-CO2H:DNR particles still remained in the dissolution chamber by weight. In vivo drug release study demonstrated that free DNR in vitreous at post-injection day 14 was 66.52 ng/mL for 95 nm pore size pSiO2-CO2H:DNR, 10.76 ng/mL for 43 nm pSi O2-CO2 H:DNR, and only 1.05 ng/mL for 15 nm pSi O2-CO2 H:DNR. Pore expansion from 15 nm to 95 nm led to a 63 folds increase of DNR release (p<0.0001) and a direct correlation between the pore size and the drug levels in the living eye vitreous was confirmed. The present study demonstrates the feasibility of regulating DNR release from pSi O2 covalently loaded with DNR by engineering the nano-pore size of pSi.

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Section: Discussionmentioning

confidence: 99%

Tunable sustained intravitreal drug delivery system for daunorubicin using oxidized porous silicon

Hou

Nieto

et al. 2014

Journal of Controlled Release

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“…Pour palier à ces différents inconvénients, d'autres équipes ont développé des implant intra-oculaires de diffusion : implant de cyclosporine + dexaméthasone [85,86], daunorubicine [87,88]. Les implants biodégradables ont l'avantage de leur dissolution spontanée avec une durée de dégradation qui dépend du type de polymère utilisé.…”

Section: Perpectives Préventivesunclassified

Prolifération vitréo-rétinienne : traitement préventif

Chiquet

Rouberol

2014

Journal Français d'Ophtalmologie

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“…It is permeable to both lipophilic and hydrophilic compounds and is well tolerated [7]. Polysulfone capillary fiber implants have only been used experimentally for carboxyfluorescein dye release and daunomycin in rabbit eyes [8, 9]. …”

Section: Drug Delivery Implant Polymersmentioning

confidence: 99%

Intravitreal Devices for the Treatment of Vitreous Inflammation

Christoforidis

Chang

Jiang

et al. 2012

Mediators of Inflammation

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The eye is a well-suited organ for local delivery of therapeutics to treat vitreous inflammation as well as other pathologic conditions that induce visual loss. Several conditions are particularly challenging to treat and often require chronic courses of therapy. The use of implantable intravitreal devices for drug delivery is an emerging field in the treatment of vitreous inflammation as well as other ophthalmologic diseases. There are unique challenges in the design of these devices which include implants, polymers, and micro- and nanoparticles. This paper reviews current and investigational drug delivery systems for treating vitreous inflammation as well as other pathologic conditions that induce visual loss. The use of nonbiodegradable devices such as polyvinyl alcohol-ethylene vinyl acetate polymers and polysulfone capillary fibers, and biodegradable devices such as polylactic acid, polyglycolic acid, and polylactic-co-glycolic acid, polycaprolactones, and polyanhydrides are reviewed. Clinically used implantable devices for therapeutic agents including ganciclovir, fluocinolone acetonide, triamcinolone acetonide, and dexamethasone are described. Finally, recently developed investigational particulate drug delivery systems in the form of liposomes, microspheres, and nanoparticles are examined.

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Effects of an Intravitreal Daunomycin Implant on Experimental Proliferative Vitreoretinopathy: Simultaneous Pharmacokinetic and Pharmacodynamic Evaluations

Cited by 22 publications

References 3 publications

Tunable sustained intravitreal drug delivery system for daunorubicin using oxidized porous silicon

Tunable sustained intravitreal drug delivery system for daunorubicin using oxidized porous silicon

Prolifération vitréo-rétinienne : traitement préventif

Intravitreal Devices for the Treatment of Vitreous Inflammation

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